rs2053456

chr2-44221493-G-Achr2-44221493-G-Cchr2-44221493-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002706.6(PPM1B):c.1134+2956G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,134 control chromosomes in the GnomAD database, including 48,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48799 hom., cov: 32)
• Consequence: PPM1B NM_002706.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

Genes affected

PPM1B (HGNC:9276): (protein phosphatase, Mg2+/Mn2+ dependent 1B) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1B	NM_002706.6	c.1134+2956G>A		intron_variant		ENST00000282412.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1B	ENST00000282412.9	c.1134+2956G>A		intron_variant		1	NM_002706.6

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121563 AN: 152016 Hom.: 48760 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 121662 AN: 152134 Hom.: 48799 Cov.: 32 AF XY: 0.797 AC XY: 59235 AN XY: 74366

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.826

Alfa AF: 0.802 Hom.: 61607

Bravo AF: 0.802

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.7
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2053456; hg19: chr2-44448632;